Gc inhibition preserves insulin sensitivity and reduces body weight without loss of muscle mass
Richard Gill, Taiyi Kuo
Richard Gill, Taiyi Kuo
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Research Article Endocrinology Metabolism

Gc inhibition preserves insulin sensitivity and reduces body weight without loss of muscle mass

Abstract

Obesity and type 2 diabetes (T2D) are metabolic diseases with increasing prevalence worldwide. Obesity often leads to T2D. Insulin resistance and impaired β cell function contribute to the onset of hyperglycemia. Previously, we reported that ablation of Gc, encoding a secreted protein with a primary role in vitamin D transport, improved pancreatic β cell function in models of diet-induced insulin resistance. Here, we show that Gc ablation had systemic insulin-sensitizing effects to prevent weight gain, hyperglycemia, and glucose intolerance; lower nonesterified fatty acids and triglycerides; and augment glucose uptake in skeletal muscle and adipose in male mice fed a high-fat diet. Interestingly, weight loss in Gc-ablated mice resulted from selective fat mass loss with preserved lean mass. Moreover, acute Gc inhibition prevented glucose intolerance caused by high-fat feeding. The data suggest that Gc inhibition can increase insulin production in β cells and insulin action in peripheral tissues, while reducing fat mass.

Authors

Richard Gill, Taiyi Kuo

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Figure 5

Indirect calorimetry in weight-matched WT and GcKO mice shows increased energy expenditure in the absence of Gc.

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Indirect calorimetry in weight-matched WT and GcKO mice shows increased ...
(A) Body weight–matched WT and GcKO mice were subjected to metabolic cages. (B–D) A group of WT (n = 6) and GcKO (n = 9) male mice were subjected to indirect calorimetry analysis, where their body weights are shown in B, fat mass shown in C, and lean mass shown in D. (E–J) Indirect calorimetry revealed oxygen consumption per light and dark cycle (E), energy expenditure per light and dark cycle (F), food intake per light and dark cycle (G) and per day (H), and food intake normalized to body weight per light and dark cycle (I) and per day (J) for WT and GcKO mice in B. Data are shown as mean ± SEM, *P < 0.05, **P < 0.01, ***P < 0.005 by Student’s t test. For E–G, and I, Student’s t test was performed at each time point between genotypes.